Drug Delivery Device

ABSTRACT

The invention relates to a drug delivery device comprising: a syringe with a body from which a needle extends and an inner sheath; a piston rod comprising a piston and an actuation head, a support sheath for holding the body. It is envisaged that the support sheath and the actuation head comprise corresponding indicators.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a U.S. National Phase Application pursuant to35 U.S.C. §371 of International Application No. PCT/EP2013/058837 filedApr. 29, 2013, which claims priority to European Patent Application No.12166720.8 filed May 4, 2012. The entire disclosure contents of theseapplications are herewith incorporated by reference into the presentapplication.

FIELD OF INVENTION

The invention relates to a drug delivery device according to thepreamble of claim 1.

BACKGROUND

Administering an injection is a process which presents a number of risksand challenges for users and healthcare professionals, both mental andphysical.

Drug delivery devices that are capable of delivering medicaments from amedication container typically designed as manual devices orauto-injectors.

In particular, with a manual device the user must provide the mechanicalenergy to drive the fluid through the needle. This is typically done byan actuation head coupled to a plunger that has to be continuouslypressed by the user during the injection. If the user stops pressing theactuation head then the injection will also stop. This means that theuser can deliver an underdose if the device is not used properly (i.e.the plunger is not fully pressed to its end position). Some manualdevices are triggered when the user pushes the actuation head completeuntil the end of the drug delivery process. Usually, the trigger force,which has to overcome, is increased compared to the pure injection forceof the drug. This increased force is only sensible on the last one toseven millimetres of the complete device stroke. Because this is on thelast millimetres of the stroke, the user gets the impression that thedrug delivery process is completed, stops pushing and therefore safetymechanisms/devices for covering the needle will not be activated.

SUMMARY

It is an object of the present invention to provide an improved drugdelivery device.

The object is achieved by a drug delivery device according to claim 1.

Preferred embodiments of the invention are given in the dependentclaims.

A drug delivery device comprises a longitudinal axis; a syringe with abody having an open proximal end and a distal end from which a needleextends and an inner sheath; a piston rod comprising a piston on adistal end and an actuation head on a proximal end, a support sheath forholding the body. The inner sheath is adapted to be movable between aretracted position in which the needle projects beyond a distal end ofthe inner sheath and an extended position in which the needle is coveredby the inner sheath. The support sheath is adapted to hold the body andto hold the inner sheath in the retracted position as well as in theextended position. The piston rod is movable from a first position inwhich the piston rod is retracted to a second position wherein a drugdelivery process is finished. The actuation head is coupled on aproximal end of the piston rod. The support sheath comprises a proximalsection, wherein the proximal section of the support sheath and theactuation head comprise corresponding indicators providing a visiblefeedback when the piston rod is in the second position.

The invention provides a user of the drug delivery device with a visibleand/or audible and/or tactile feedback about the current state of a drugdelivery process, in particular to inform the user that the dose of drugwas fully delivered so the user can remove the drug delivery device fromthe injection site, whereby safety features of the drug delivery device,e.g. features to cover the needle, can be activated.

In an exemplary embodiment, the corresponding indicators are designed ascoloured and/or tactile markings so as to help the user to get a visibleand/or tactile feedback about the current state of the drug deliveryprocess.

In an exemplary embodiment, the coloured and/or tactile markings areformed as fragmented markings and/or circumferential markings, wherebythe actuation head comprises a number of fragmented markings and atleast one circumferential marking and the support sheath comprises atleast one circumferential marking. For example, the fragmented markingsare designed as printed or moulded arrows and pointed towards thecircumferential marking arranged on the actuation head, whereby thecircumferential marking is designed as a printed or mouldedcircumferential line. When the piston rod is pressed down by applicationof a sufficient force on the actuation head the circumferential markingsof the support sheath and the actuation head come together.Alternatively, the actuation head and the support sheath respectivelycomprise at least one circumferential marking or respectively a numberof fragmented markings

For an alternative or additional tactile feedback, the actuation headand the support sheath comprise corresponding circumferential latchingelements, for example the support sheath comprise a circumferentialrecess that is suitable to receive a circumferential bulging arranged onthe actuation head.

In an exemplary embodiment, the support sheath is made from an opticallytransparent material and the actuation head is made from an opticallyintransparent coloured material, whereby the colour of the material ofthe actuation head differs from the colour of the fragmented and/orcircumferential markings so that they are clearly visible for a user. Inan alternative embodiment, a finger flange part of the syringe may betransparent and a plunger of the syringe may be made from a colouredmaterial, e.g. in a signal colour. This embodiment also allows forindicating the current state of the injection.

In another exemplary embodiment, the coloured markings are formedrespectively as a material colouration, whereby the material of thesupport sheath is designed at least section wise as a colouredtranslucent material or as an optically intransparent coloured materialor as a transparent material, whereby the degree of transparency orcolour of the translucent material and/or the intransparent material ofthe support sheath is substantially equal to the degree of transparencyor colour of the material of the actuation head. Advantageously, withthe translucent material the design of the drug delivery device looksvisually appealing and further enables an optical scanning during theproduction process.

In another exemplary embodiment the tactile markings may be formedrespectively as a surface modification, in particular a grain.

Furthermore, in another exemplary embodiment, the correspondingindicators are designed as positive locking elements, whereby a firstlocking element is formed by a circumferential end portion of theactuation head extending in a distal direction, and a second positivelocking element that is formed by a proximal section of the supportsheath extending in a proximal direction.

In an exemplary embodiment, the first locking element comprises an outercircumference smaller than an inner circumference of the second positivelocking element, so that the first locking element will join into thesupport sheath when the plunger rod is pressed down. To give the user afeedback for the end of drug delivery in an easy way, the first lockingelement comprises a substantially annular portion that extendsperpendicular with respect to the longitudinal axis in such a manner,that a circumference of the annular portion is equal or larger than anouter circumference of the second positive locking element. This enablesa visible, audible and/or tactile feedback for the user, because theannular portion abuts against the second locking element when drugdelivery is finished. For the user it seems that a gap between theactuation head and the support sheath is closed if the stroke iscompleted. The drug delivery device looks then closed for the user. Thelocking element may be configured as one or more circumferentialsegments or a complete circumferential clip geometry.

In an exemplary embodiment the piston rod is movable between a retractedfirst position prior to drug delivery and a second position aftercomplete drug delivery, wherein in the second position the annularportion either abuts against the second locking element or wherein theannular portion remains axially spaced from the second locking elementby a maximal distance of 3 mm, in particular between 0.1 mm and 3 mm.

In an alternatively exemplary embodiment, the first locking element isdesigned with a double wall, whereby an outer wall comprises an innercircumference larger than the outer circumference of the second positivelocking element, whereby an inner wall comprises an outer circumferencesmaller than the inner circumference of the second positive lockingelement, and whereby a recess arranged between the outer wall and theinner wall is formed corresponding to the second positive lockingelement. This enables a visible and tactile feedback for the user,whereby the actuation head completely overlaps the circumferentialportion of the support sheath when drug delivery is finished.

To give the user an additional audible feedback, an exemplary embodimentof the invention provides, that an inner surface of the outer wallcomprises at least one first latching element that corresponds to asecond latching element arranged on an outer surface of the secondpositive locking element.

In a further exemplary embodiment, the first latching element isdesigned as a latching nose, whereby the second latching element isdesigned as a latching recess, and whereby the latching recess isadapted to receive the latching nose at the end of a drug deliveryprocess. With this, the user gets an “audible click” feedback that drugdelivery is finished. Moreover, this provides an indication of use as a“lock in” of the actuation head in the support sheath as to preventreuse.

In an exemplary embodiment, the second positive locking elementcomprises a number of spring elements suitable for being inactivated toretain the inner sheath in a retracted position inside the supportsheath and for being activated to allow the inner sheath to move in thedistal direction towards an extended position. In the mind of theinvention, the retracted position of the inner sheath is defined as aposition, in which the needle is exposed, whereby the extended positionof the inner sheath is defined as a position, in which the needle iscovered by the inner sheath. Preferably, the spring elements ensure thatthe inner sheath is controlled in a manner that is reliable and painlessfor the user.

In an exemplary embodiment, the spring elements are designed as firstresilient tongues that are integral with an inner surface of the secondpositive locking element and suitable for being moved resiliently froman inactive position to an active position, in which they release theinner sheath from the support sheath, whereby the first resilienttongues are urged towards the active position by a distal movement ofthe actuation head. This embodiment of the invention provides that theuser does not need to perform any additional movement at the end of drugdelivery to enable the inner sheath to be extended.

In an exemplary embodiment, the first resilient tongues abut against anumber of further spring elements arranged on the inner sheath, wherebythe further spring elements are designed as second resilient tongues andheld within the support sheath in a snap-fastening manner.Advantageously, the inner sheath is thus held in position in an easy andsafety way.

In an exemplary embodiment, the second resilient tongues are resilientlymoved inside the support sheath when the first resilient tongues aremoved towards their active position, whereby the snap-fit connection ofthe inner sheath and the support sheath releases. This provides that nospecial precautions need to be taken as to how the fingers arepositioned on the support sheath and on the actuation head in order toensure that the inner sheath will move to extend over the needle.

For holding the drug delivery device comfortably, at least two fingerflanges are arranged on the support sheath and extend perpendicular withrespect to the longitudinal axis. In an alternative embodiment, onecircular finger flange may be arranged. Thereby, the user can handle thedevice with two fingers positioned against the finger flanges and onethumb on the actuation head for moving the piston rod. In the secondposition of the piston rod the finger flanges either abut against thefirst locking element or the finger flanges remain axially spaced fromthe first locking element by a maximal distance of 3 mm, in particularbetween 0.1 mm and 3 mm.

The term “drug” or “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exendin-3 or exendin-4 or an analogue or derivative ofexendin-3 or exendin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 Exendin-4(1-39),

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group-Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150 kDa) that are also knownas immunoglobulins which share a basic structure. As they have sugarchains added to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and δ approximately 500 amino acids, whileμ and ε have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (C_(H)) and the variable region (V_(H)). Inone species, the constant region is essentially identical in allantibodies of the same isotype, but differs in antibodies of differentisotypes. Heavy chains γ, α and δ have a constant region composed ofthree tandem Ig domains, and a hinge region for added flexibility; heavychains μ and ε have a constant region composed of four immunoglobulindomains. The variable region of the heavy chain differs in antibodiesproduced by different B cells, but is the same for all antibodiesproduced by a single B cell or B cell clone. The variable region of eachheavy chain is approximately 110 amino acids long and is composed of asingle Ig domain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab')2 fragment containingboth Fab pieces and the hinge region, including the H-H interchaindisulfide bond. F(ab')2 is divalent for antigen binding. The disulfidebond of F(ab')2 may be cleaved in order to obtain Fab'. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will become more fully understood from thedetailed description given hereinbelow and the accompanying drawingswhich are given by way of illustration only, and thus, are not limitiveof the present invention, and wherein:

FIG. 1 shows a perspective view of a part of a drug delivery device witha support sheath and an actuation head comprising corresponding colouredmarkings in a first embodiment,

FIG. 2 shows a perspective view of a part of a drug delivery device witha support sheath and an actuation head comprising corresponding colouredmarkings in a second embodiment,

FIG. 3 shows a perspective view of a part of a drug delivery device witha support sheath and an actuation head comprising corresponding colouredmarkings in a third embodiment,

FIG. 4 shows a perspective view of the drug delivery device with asupport sheath and a piston rod coupled to an actuation head comprisingcorresponding positive locking elements in a first embodiment, wherebythe piston rod is in a first position,

FIG. 5 shows a perspective view of the drug delivery device according toFIG. 4, whereby the piston rod is in a second position

FIG. 6 shows a part of a sectional view of the drug delivery deviceaccording to FIG. 5,

FIG. 7 shows a side view of a drug delivery device with correspondingpositive locking elements in a second embodiment,

FIG. 8 shows a part of a sectional view of the drug delivery deviceaccording to FIG. 7,

FIG. 9 shows a perspective view of a drug delivery device withcorresponding positive locking elements, whereby the piston rod is in afirst position,

FIG. 10 shows a perspective view of the drug delivery device accordingto FIG. 9, whereby the piston rod is in a second position,

FIG. 11 shows a part of a sectional view of the drug delivery deviceaccording to FIG. 10,

FIG. 12 shows a part of a sectional view of a drug delivery device withcorresponding positive elements in the third embodiment and withlatching elements,

FIG. 13 shows a perspective view of a part of the drug delivery deviceaccording to the FIGS. 11 and 12 without actuation head and with anouter contour of a second positive locking element in a firstembodiment,

FIG. 14 shows a perspective view of a part of the drug delivery devicewith a outer contour of the second positive locking element in a secondembodiment, whereby the piston rod is in the second position,

FIG. 15 shows a part of a sectional view of a drug delivery device withcorresponding positive locking elements in the third embodiment,latching elements, and second spring elements, and.

FIG. 16 shows an exploded illustration of a sectional view of a drugdelivery device.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

FIGS. 1 to 3 respectively show a part of a drug delivery device 1defining a longitudinal axis A. In the following the drug deliverydevice 1 is considered generally as a device capable of deliveringmedicaments to a patient in a manual way. The drug delivery device 1comprises a support sheath 2 and a piston rod 3 that is coupled with anactuation head 4 on a proximal end thereof

The support sheath 2 is divided into two sections 2.1, 2.2, inparticular in a distal section 2.1 designed as a substantially tubularbody, and a proximal section 2.2 having a larger diameter than thedistal section 2.1.

The proximal section 2.2 can be also described as a circumferential endsection of the support sheath 2 that extends parallel to the axis A in aproximal direction P. In the exemplary embodiments of the invention,shown in the FIGS. 1 to 3, an inner periphery of the proximal section2.2 is suitable to receive a circumferential end portion 4.1 of theactuation head 4 that extends parallel to the axis A in a distaldirection D.

Further, the drug delivery device 1 comprises a syringe 5 with a body5.1 designed as a cartridge respectively pre-filled with a liquidmedicament component. The body 5.1 includes an open proximal end and adistal end from which a needle 6 extends. Furthermore, the body 5.1 isheld within an inner sheath 7 and is conventionally formed as asubstantially tubular body, being made of glass or of plastics material.

The inner sheath 7 is generally in a refracted position inside thesupport sheath 2 when the piston rod 3 is in a first position, whereinthe piston rod 3 is retracted and the drug device 1 is ready for a drugdelivery process. The body 5.1 is engaged within the inner sheath 7 andis held relative to the support sheath 2 in such a manner that theneedle 6 projects beyond a distal end 2.1 of the support sheath 2 and adistal end 7.1 of the inner sheath 7.

When the piston rod 3 is in a second position, wherein the drug deliveryprocess is finished, i.e. drug is completely delivered; the inner sheath7 is in an extended position, in which the needle 6 is covered by theinner sheath 7. The body 5.1 is then held within the support sheath 2.

Moreover, the drug delivery device 1 comprises a first spring element10, preferably designed as a helical spring that is compressed when theinner sheath 7 is retained in the retracted position and that urges theinner sheath 7 to move from the retracted position towards the extendedposition by relaxing of it. Therefore the first spring element 10 bearsagainst the inner sheath 7 in the distal direction D and against thesupport sheath 2 in the proximal direction P.

The coupling of the body 5.1 and the inner sheath 7 respective with thesupport sheath 2 will be described in more detail in the description ofFIG. 15.

To provide a user of the drug delivery device 1 with a visible and/ortactile feedback about the current state of the drug delivery process,in particular to inform the user that the dose of drug was fullydelivered so the user can remove the drug delivery device 1 from apatient site, the actuation head 4 and the support sheath 2 comprisecorresponding coloured and/or tactile markings 8 as indicators.

In a first embodiment shown in FIG. 1, the coloured and/or tactilemarkings 8 are designed as fragmented and circumferential markings. Theactuation head 4 comprises a number of printed or moulded arrows asfragmented markings and one circumferential line as the circumferentialmarking The support sheath 2 comprises one circumferential line ascircumferential marking.

In a second embodiment shown in FIG. 2, the coloured and/or tactilemarkings 8 are designed respectively as printed or mouldedcircumferential lines. In a third embodiment illustrated in FIG. 3, thecoloured and/or tactile markings 8 are designed respectively asfragmented lines in the form of a number of printed or moulded squares.

When the piston rod 3 is pressed down by application of a sufficientforce on a bearing surface 4.2 of the actuation head 4 the colouredand/or tactile markings 8 of the support sheath 2 and the actuation head4 come together. Pressing down the piston rod 3 means that it is movedfrom the first position towards the second position.

For an alternative or additional tactile feedback, the actuation head 4and the support sheath 2 comprise corresponding circumferential latchingelements (not shown). In an example, the support sheath 2 comprises acircumferential recess that is suitable to receive a circumferentialbulging arranged on the actuation head 4.

In a further exemplary embodiment of the invention the support sheath 2is made from an optically transparent material, whereby the actuationhead 4 is made from an optically intransparent coloured material.Preferably, the colour of the material of the actuation head 4 differsfrom the colour of the coloured and/or tactile markings 8 so that theyare clearly visible for the user. For example, the material of theactuation head 4 comprises is designed with a green colour and thecircumferential and/or fragmented markings include a blue colour.

It goes without saying that the coloured and/or tactile markings 8described in the above embodiments can be designed as any othergeometric form suitable to give a user a clearly visible feedback.

In another embodiment of the invention (not shown in any of the FIGS. 1to 15), the material of the support sheath 2 is designed at leastsection wise as a coloured translucent material or as an opticallyintransparent coloured material. Preferably, a colour of the translucentmaterial and/or the intransparent material of the support sheath 2 issubstantially equal to the colour of the material of the actuation head4.

The FIGS. 4 to 15 show the drug delivery device 1 with correspondingpositive locking elements 9.1, 9.2 in different embodiments asindicators. The FIGS. 4 to 6 show the drug delivery device 1 with thepositive locking elements 9.1, 9.2 in a first embodiment.

A first locking element 9.1 is formed by the circumferential end portion4.1 of the actuation head 4; a second positive locking element 9.2 isformed by the proximal section 2.2 of the support sheath 2.

According to the first embodiment, the first locking element 9.1comprises an outer circumference smaller than an inner circumference ofthe second positive locking element 9.2, so that the first lockingelement 9.1 will join into the second positive locking element 9.2 ifthe piston rod 3 is moved from the first position, illustrated in FIG.4, to the second position, illustrated in the FIGS. 5 to 7.

Further, the first locking element 9.1 comprises a substantially annularportion 9.1.1, e.g. a ring, which is arranged proximally and extendsperpendicular with respect to the axis A.

A circumference of the annular portion 9.1.1 is equal or larger than anouter circumference of the second positive locking element 9.2.Likewise, the circumference of the annular portion 9.1.1 may be smallerthan the outer circumference but greater than the inner circumference ofthe second positive locking element 9.2. The annular portion 9.1.1 ispreferably integral with the actuation head 4 to enable effective costsand maintain regarding to a production process.

The annular portion 9.1.1 abuts against the second locking element 9.2when the piston rod 3 is in the second position. This enables a visibleand tactile feedback for the user when drug is fully delivered.Likewise, a distal edge of the first locking element 9.1 may abutagainst the second locking element 9.2 when the piston rod 3 is in thesecond position, while the annular portion 9.1.1 may remain axiallyspaced from the second locking element 9.2, e.g. by a distance between0.1 mm and 3 mm. This may lead the user to fully depress the piston rod3 thereby triggering the inner sheath 7.

The FIGS. 7 and 8 show the positive locking elements 9.1, 9.2 in asecond embodiment, wherein the first positive locking element 9.1comprises a proximal end portion 9.1.2 with a circumference equal to orlarger than the inner circumference of the second positive lockingelement 9.2. The proximal end portion 9.1.2 abuts against the secondlocking element 9.2 when the piston rod 3 is in the second positionequivalent as it is performed by the annular portion 9.1.1.

The FIGS. 9 to 15 show the drug delivery device 1 with positive lockingelements 9.1, 9.2 in a third embodiment, whereby in FIG. 9 the pistonrod 3 is retained in the first position and in the FIGS. 10 and 11 thepiston rod 3 is retained in the second position.

The first positive locking element 9.1 is designed with a double wall.An outer wall 9.1.3 comprises an inner circumference larger than theouter circumference of the second positive locking element 9.2 and aninner wall 9.1.4 comprises an outer circumference smaller than the innercircumference of the second positive locking element 9.2.

The outer and inner wall 9.1.3, 9.1.4 are spaced apart from each other,hence defining a recess 9.1.5 between, which is formed corresponding toa contour of the second positive locking element 9.2.

When the piston rod 3 is moved from the first position to the secondposition, the first positive locking element 9.1 moves over the secondpositive locking element 9.2 in such a manner that the outer wall 9.1.3moves over the outer surface of the second positive locking element 9.2and the inner wall 9.1.4 moves over an inside surface of the secondpositive locking element 9.2.

At the same time the recess 9.1.5 receives the contour of the secondpositive locking element 9.2. With this, the first positive lockingelement 9.1 hides the second positive locking element 9.2 when thepiston rod 3 is in the second position. The end of drug delivery is thenpractically indicated when the circumferential end portion 4.1 is movedcompletely over the proximal section 2.2 of the support sheath 2. Thiscorresponds to a visible feedback.

For an additional audible feedback, the FIGS. 12 and 13 show anexemplary embodiment of the invention, wherein an inner surface of theouter wall 9.1.3 comprises a first latching element 9.1.3.1, illustratedin the sectional view of FIG. 12. The first latching element 9.1.3.1 isarranged distally and comprises at least one latching nose 9.1.3.1.1that is suitable to latch into a corresponding second latching element9.2.1 arranged distally on an outer surface of the second positivelocking element 9.2 and that comprises at least one latching recess9.2.1.1.

In the terminology of the invention the inner surface of the outer wall9.1.3 is a surface that is faced towards the inner wall 9.1.4, wherebyan inner surface of the inner wall 9.1.4 is a surface faced towards theouter wall 9.1.3.

FIG. 13 illustrates the second positive locking element 9.2 in aperspective view so that two latching recesses 9.2.1.1, spaced apartfrom each other in a peripheral direction, are visible in more detail.Preferably, the second positive locking element 9.2 comprises twoadditional latching recesses 9.2.1.1 (not shown) arranged oppositely tothe illustrated latching recesses 9.2.1.1. Hence, the outer wall 9.1.3of the first positive locking element 9.1 comprises four latching noses9.1.3.1.1.

It goes without saying that the illustrated embodiment in FIG. 13 onlyshows an exemplary embodiment of the invention. The correspondinglatching elements 9.1.3.1, 9.2.1 can comprise a number of latching noses9.1.3.1.1 respectively latching recesses 9.2.1.1 differing from thatwhat is described above. Further, the first latching element 9.1.3.1 canbe designed as a circumferential bulging that latches into the secondlatching element 9.2.1 designed as a corresponding circumferentialrecess.

When the piston rod 3 is moved from the first position to the secondposition and hence the outer wall 9.1.3 moves over the outer surface ofthe second positive locking element 9.2 the latching noses 9.1.3.1.1latch into the corresponding latching recesses 9.2.1.1. This provides afeedback in the form of an audible click when drug delivery is finishedand an indication of use as a “lock in” of the actuation head 4 in thesupport sheath 2 as to prevent reuse.

As can be seen further in FIG. 13 (and also in the FIGS. 4, 5 and 9),the second positive locking element 9.2 comprises a number of curvatures9.2.2 that corresponds to the number of latching recesses 9.2.1.1,whereby the curvatures 9.2.2 are arranged in the area of the latchingrecesses 9.2.1.1. Preferably, the outer and inner wall 9.1.3, 9.1.4 ofthe first positive locking element 9.1, in particular the inner surfaceof the outer wall 9.1.3 and an inner surface of the inner wall 9.1.4,comprise corresponding forms to enable an optimal positive locking fitbetween the first and second positive locking elements 9.1, 9.2.

FIG. 14 shows an alternative embodiment of the invention, in which thefirst positive locking element 9.1 comprises a substantially round outercontour. Even it is not illustrated; the second positive locking element9.2 comprises a corresponding form without the curvatures 9.2.2 shown inFIG. 13. This enables an easy performance of a production process of thedrug delivery device 1.

For holding the drug delivery device 1 comfortably, the support sheath 2comprises two finger flanges 9.2.3 that are illustrated best in FIG. 14.The finger flanges 9.2.3 are arranged distally on the second positivelocking element 9.2 and extend perpendicular with respect to the axis A.Thereby, the user can handle the drug delivery device 1 between theindex and middle fingers, placing these fingers against the fingerflanges 9.2.3 and driving the piston rod 3 by pressing the thumb on theactuation head 4.

In an alternative embodiment a circular finger flange can be arranged.

In FIG. 15, a safety mechanism of the drug delivery device 1 is shown inmore detail. The safety mechanism enables that the inner sheath 7 ismovable from the retracted position to the extended position, in which adistal tip 6.1 of the needle 6 is covered completely by the inner sheath7.

Therefore, the second positive locking element 9.2 comprises a number ofsecond spring elements 11 designed as resilient tongues, following namedas first resilient tongues 11.1, which are integral with an innersurface of the second positive locking element 9.2.

The first resilient tongues 11.1 are directed inwards and build a rampsurface for the first positive locking element 9.1 directed outwards,when the piston rod 3 is moved towards the second position.

A free end 11.1.1 of the first resilient tongues 11.1 abut against thirdspring elements 12 arranged on the inner sheath 7. The third springelements 12 are designed as resilient tongues, following named as secondresilient tongues 12.1 that tend naturally to spread apart slightly,going away from the axis A. In the example shown, the second resilienttongues 12.1 are integral with the inner sheath 7 and hook onto thesupport sheath 2, in particular the proximal section 2.2 that comprisestherefore corresponding nuts 2.3.

The first resilient tongues 11.1 are suitable for being movedresiliently from an inactive position, in which they abut against thesecond resilient tongues 12.1 without prestressing the second resilienttongues 12.1, to an active position, in which they release the innersheath 7 from the support sheath 2.

For releasing the inner sheath 7 the second resilient tongues 12.1 areurged by the first resilient tongues 11.1 to move resiliently inside thesupport sheath 2 by a distal movement of the piston rod 3. Inparticular, when the inner wall 9.1.4 of the first positive lockingelement 9.1 has moved over the ramp surface of the first resilienttongues 11.1 it abuts against an end 11.1.2 of the first resilienttongues 11.1 that is arranged on the inner surface of the secondpositive locking element 9.2.

This abutting causes a resilient movement of the first resilient tongues11.1 inside the support sheath 2 which in turn causes that the secondresilient tongues 12.1 are resiliently moved inside the support sheath 2releasing the inner sheath 7 from the support sheath 2.

Therefore, the end 11.1.2 of the first resilient tongues 11.1 comprisesa material weakness compared to the free end 11.1.1. According to adistal direction D, behind the material weakness a projection 13 isarranged on the second positive locking element 9.2 that projects in theproximal direction P. When the inner wall 9.1.4 abuts against thematerial weakness and thus the first resilient tongues 11.1 movedresiliently inside the support sheath 2 the material weakness of thefirst resilient tongues 11.1 abuts against the projection 13. Thisenables a good “rolling up” of the first resilient tongues 11.1 on theprojection 13 so that a risk for damages of the first resilient tongues11.1 is reduced.

Thus, the actuation head 4 actuated the first resilient tongues 11.1 torelease the inner sheath 7. The first spring element 10 thrust the innersheath 7 forward into the distal direction D so that it projects wellbeyond the distal section 2.1 of the support sheath 2 over a lengthsuitable for forming a protective shield around the distal tip 6.1 ofthe needle 6. Thus, a risk for a user to come in contact with the needle6 after drug delivery is reduced.

The inner sheath 7 is retained in the extended position by coming intoabutment against a shoulder 2.1.1 formed into the support sheath 2.Therefore, FIG. 16 shows a drug delivery device 1 in an exploded view.As can be seen a proximal end of the second resilient tongues 12.1 abutsagainst the shoulder 2.1.1 in the proximal direction P when the innersheath 7 is retained in the extended position. Thus a proximal movementof the inner sheath 7 is limited when the second resilient tongues 12.1passes the shoulder 2.1.1. With this the inner sheath 7 is prevented forbeing refracted into the support sheath 2 and to expose the needle 6.The resilient tongues 12.1 flex outwards against the support sheath 2 sothat they always interfere with the shoulder 2.1.1 thus providingreliable safety.

The body 5.1 is held relative to the support sheath 2 in a not shown wayby holding elements belonging to the support sheath 2, co-operating witha proximal end of the body 5.1.

1-17. (canceled)
 18. Drug delivery device comprising: a syringe with abody from which a needle extends, an inner sheath adapted to be movablebetween a retracted position in which the needle projects beyond adistal end of the inner sheath and an extended position in which theneedle is covered by the inner sheath; a support sheath adapted to holdthe body and to hold the inner sheath in the retracted position as wellas in the extended position, a piston rod comprising a piston, whereinthe piston rod is movable from a first position in which the piston rodis retracted to a second position wherein a drug delivery process isfinished, and an actuation head, characterized in that the actuationhead is coupled on a proximal end of the piston rod, the support sheathcomprises a proximal section, wherein the proximal section of thesupport sheath and the actuation head comprise corresponding indicatorsproviding a visible feedback when the piston rod is in the secondposition.
 19. Drug delivery device according to claim 18, characterizedin that the corresponding indicators are designed as correspondingpositive locking elements, whereby a first positive locking element isformed by a circumferential end portion of the actuation head extendingin a distal direction (D), and a second positive locking element formedby a proximal section of the support sheath extending in a proximaldirection.
 20. Drug delivery device according to claim 19, characterizedin that the first locking element comprises an outer circumferencesmaller than an inner circumference of the second positive lockingelement, and a substantially annular portion that extends perpendicularwith respect to the longitudinal axis (A) of the drug delivery device insuch a manner that a circumference of the annular portion is equal orlarger than an outer circumference of the second positive lockingelement.
 21. Drug delivery device according to claim 20, characterizedin that the piston rod is movable between a retracted first positionprior to drug delivery and a second position after complete drugdelivery, wherein in the second position the annular portion eitherabuts against the second locking element or wherein the annular portionremains axially spaced from the second locking element by a maximaldistance of 3 mm.
 22. Drug delivery device according to claim 20,characterized in that the first locking element is designed with adouble wall, whereby an outer wall comprises an inner circumferencelarger than the outer circumference of the second positive lockingelement, whereby an inner wall comprises an outer circumference smallerthan the inner circumference of the second positive locking element, andwhereby a recess arranged between the outer wall and the inner wall isformed corresponding to the second positive locking element.
 23. Drugdelivery device according to claim 22, characterized in that an innersurface of the outer wall comprises at least one first latching elementthat corresponds to a second latching element arranged on an outersurface of the second positive locking element.
 24. Drug delivery deviceaccording to claim 23, characterized in that the first latching elementis designed as a latching nose or a number of latching nose segments ora circumferential clip, whereby the second latching element is designedas a corresponding latching recess, and whereby the latching recess isadapted to receive the first latching element nose at the end of a drugdelivery process.
 25. Drug delivery device according to claim 19,characterized in that the second positive locking element comprises anumber of spring elements suitable for being deactivated to retain theinner sheath in a retracted position inside the support sheath and forbeing activated to allow the inner sheath to move in the distaldirection (D) towards an extended position.
 26. Drug delivery deviceaccording to claim 25, characterized in that the spring elements aredesigned as first resilient tongues that are integral with an innersurface of the second positive locking element.
 27. Drug delivery deviceaccording to claim 26, characterized in that the first resilient tonguesabut against a number of further spring elements arranged on the innersheath, whereby the further spring elements are designed as secondresilient tongues that are held within the support sheath in asnap-fastening manner.
 28. Drug delivery device according to claim 27,characterized in that the second resilient tongues are resiliently movedinside the support sheath when the first resilient tongues are movedtowards their inactive position, whereby the snap-fit connection of theinner sheath and the support sheath releases.
 29. Drug delivery deviceaccording to claim 18, characterized in that the correspondingindicators are designed as coloured or tactile markings
 30. Drugdelivery device according to claim 29, characterized in that themarkings are formed as fragmented markings and/or circumferentialmarkings, whereby the actuation head comprises a number of fragmentedmarkings and at least one circumferential marking and the support sheathcomprises at least one circumferential marking, or whereby the actuationhead and the support sheath respectively comprise at least onecircumferential marking or respectively a number of fragmented markings.31. Drug delivery device according to claim 30, characterized in thatthe support sheath is made from an optically transparent material andthat the actuation head is made from an optically intransparent colouredmaterial, whereby the colour of the material of the actuation headdiffers from the colour of the fragmented and/or circumferentialmarkings.
 32. Drug delivery device according to claim 29, characterizedin that the coloured and/or tactile markings are formed respectively asa material colouration, whereby the material of the support sheath isdesigned at least section-wise as a coloured translucent material or asan optically intransparent coloured material or as a transparentmaterial, whereby the degree of transparency or colour of thetranslucent material and/or intransparent material of the support sheathis substantially equal to the degree of transparency or colour of thematerial of the actuation head.
 33. Drug delivery device according toclaim 29, characterized in that the tactile markings are formedrespectively as a surface modification, in particular a grain.
 34. Drugdelivery device according to claim 18, characterized in at least twofinger flanges or a circular finger flange arranged on the supportsheath and extending perpendicular with respect to the longitudinal axis(A) of the drug delivery device, wherein in the second position of thepiston rod the finger flanges either abut against the first lockingelement or wherein the finger flanges remain axially spaced from thefirst locking element by a maximal distance of 3 mm.